Late infantile neuronal ceroid lipofuscinosis is due to splicing mutationsin the CLN2 gene

Late infantile neuronal ceroid lipofuscinosis, LINCL, is one of the most co mmon pediatric neurodegenerative disorders. It is caused by mutations in th e CLN2 gene, which encodes a lysosomal pepstatin-insensitive peptidase (LPI P). We have identified a novel mutation, T523-1G --> A, by molecular analys es of three unrelated LINCL cases. The mutation was found to affect a 3' in tronic splicing acceptor site, resulting in an aberrant mRNA with an insert ion of 146 bp of intronic sequence. This causes a frame shift, produces a n onfunctional truncated protein, and results in LINCL. (C) 1999 Academic Pre ss.